This invention relates to new chemical compounds, and more particularly it relates to derivatives of propenamide, 2-methylpropenamide, 2-butenamide, 2-methyl-2-butenamide and cyclopropanecarboxamide. Said derivatives are substituted on the nitrogen atom by an alkyl or cycloalkyl group. Additionally, said propenamide, 2-methylpropenamide, 2-butenamide and 2-methyl-2-butenamide derivatives are further substituted at the 3-position by a (4-carboxy-2-oxo-pyrrolidino)phenyl group, and said cyclopropanecarboxamide derivatives are further substituted at the 2-position by a (4-carboxy-2-oxo-pyrrolidino)phenyl group. These compounds are useful as antagonists of the slow-reacting substance of anaphylaxis (SRS-A).
It is known that certain substances, known as mediators of anaphylaxis, play an important role in inducing an allergic reaction, such as bronchospastic attack or allergic rhinitis, in a human subject. Two examples of such mediators are histamine and the slow-reacting substance of anaphylaxis (SRS-A), the latter substance being a very important mediator in allergic bronchial asthma. SRS-A is a substance which is synthesized and released in or near target tissues, in a sensitive (allergic) human subject, shortly after challenge with the appropriate antigen. The human bronchus is particularly sensitive to SRS-A.
Rational approaches to drug therapy to prevent, remove or ameliorate the symptoms of allergic reactions have focussed on either blocking the release of mediators of anaphylaxis, or, on the other hand, on antagonizing their effects. Disodium cromoglycate (The Merck Index, Merck and Co., Inc., Rahway, N.J., 9th Edition, 1976, 2585) is a drug which has recently been introduced and which blocks the release of mediators of anaphylaxis, and commercially available drugs which antagonize histamine (antihistamines) are well-known (e.g. methapyrilene, diphenhydramine, chlorpheniramine). Conversely, there is a paucity of substances known which antagonize SRS-A, and none of them is used in clinical practice today. One agent has been widely studied (FPL 55712--Agents and Actions, 9, 133 [1979]).